Association of CYP3A5 Expression and Vincristine Neurotoxicity in Pediatric Malignancies in Turkish Population

Vincristine is a widely used chemotherapeutic agent in the treatment of childhood malignancies. Neuropathy is the most common adverse effect. CYP3A4 and CYP3A5 enzymes of cytochrome p450 enzyme system are responsible in vincristine metabolism. Genetic polymorphism may alter the vincristine metabolis...

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Published in:	Journal of pediatric hematology/oncology Vol. 39; no. 6; pp. 458 - 462
Main Authors:	Kayilioğlu, Hülya, Kocak, Ulker, Kan Karaer, Derya, Percin, Emriye F, Sal, Ertan, Tekkesin, Funda, Isik, Melek, Oner, Nergiz, Belen, Fatma B, Yilmaz Keskin, Ebru, Okur, Arzu, Albayrak, Meryem, Kaya, Zuhre, Pinarli, Faruk G, Yenicesu, Idil, Karadeniz, Ceyda, Oguz, Aynur, Gursel, Turkiz
Format:	Journal Article
Language:	English
Published:	United States 01-08-2017
Subjects:	Adolescent Antineoplastic Agents, Phytogenic - adverse effects Antineoplastic Agents, Phytogenic - therapeutic use Case-Control Studies Child Child, Preschool Cytochrome P-450 CYP3A - genetics Dose-Response Relationship, Drug Genotype Humans Infant Neoplasms - complications Neoplasms - drug therapy Neoplasms - genetics Neurotoxicity Syndromes - etiology Precursor Cell Lymphoblastic Leukemia-Lymphoma - complications Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics Turkey Vincristine - adverse effects Vincristine - therapeutic use
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Summary:	Vincristine is a widely used chemotherapeutic agent in the treatment of childhood malignancies. Neuropathy is the most common adverse effect. CYP3A4 and CYP3A5 enzymes of cytochrome p450 enzyme system are responsible in vincristine metabolism. Genetic polymorphism may alter the vincristine metabolism and the neurotoxicity rate. In this study, distribution of CYP3A5 alleles among Turkish children with malignancies, relation between CYP3A5 genotype and neurotoxicity rates, as well as severity and duration of neuropathy and total vincristine doses were investigated. Patient group consisted of 115 patients (age, 1 to 17 y) with acute lymphoblastic leukemia and solid tumors, who were treated with vincristine consisting chemotherapy protocols. Control group consisted of 50 children without any neurological symptom or disorders. All patient files were reviewed for presence and severeness of neurotoxicity symptoms. Blood samples were obtained and CYP3A5 genotypes were analyzed. Neurotoxicity occurred in 20.8% of patients. Although it was found to occur more frequently after 4 doses of vincristine, and rates were higher in the low-dose vincristine group suggesting other contributing factors. Although neurotoxicity rate in the CYP3A51/3 genotype was 17.6%, it was 21.6% in the CYP3A53/3 genotype and the difference was not statistically significant (P<0.05). This study suggested that vincristine-related neurotoxicity is dose-independent and genotype is not the only causative factor in the occurrence of neurotoxicity in these patients.
ISSN:	1077-4114 1536-3678
DOI:	10.1097/MPH.0000000000000910